title: Mid- and late-life diabetes in relation to the risk of dementia: a population-based twin study.
abstract: OBJECTIVE
  We aimed to verify the association between diabetes and the risk of dementia, Alzheimer's disease, and vascular dementia in twins and to explore whether genetic and early-life environmental factors could contribute to this association.
  
  
  METHODS
  This study included 13,693 twin individuals aged > or =65 years. Dementia was diagnosed according to DSM-IV (Diagnostic Manual of Mental Disorders, 4th ed.) criteria. Information on diabetes was collected from the inpatient registry and self- or informant-reported history of diabetes. Data were analyzed following two strategies: 1) unmatched case-control analysis for all participants using generalized estimating equation (GEE) models and 2) cotwin matched case-control analysis for dementia-discordant twin pairs using conditional logistic regression.
  
  
  RESULTS
  Of all participants, 467 were diagnosed with dementia, including 292 with Alzheimer's disease and 105 with vascular dementia, and an additional 170 were diagnosed with questionable dementia. Diabetes was present in 1,396 subjects. In GEE models, diabetes was associated with adjusted odds ratios (ORs) (95% CI) of 1.89 (1.51-2.38) for dementia, 1.69 (1.16-2.36) for Alzheimer's disease, and 2.17 (1.36-3.47) for vascular dementia. Compared with late-life diabetes (onset age > or =65 years), the risk effect of mid-life diabetes (onset age <65 years) on dementia was stronger. Conditional logistic analysis of 210 dementia-discordant twin pairs led to ORs of 2.41 (1.05-5.51) and 0.68 (0.30-1.53) for dementia related to mid- and late-life diabetes, respectively.
  
  
  CONCLUSIONS
  Diabetes increases the risk of Alzheimer disease and vascular dementia. The risk is stronger when diabetes occurs at mid-life than in late life. Genetic and early-life environmental factors might contribute to the late-life diabetes-dementia association but could not account for the mid-life diabetes-dementia association.
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Aging Research Center, Karolinska Institutet and Stockholm Gerontology Research Center, Stockholm, Sweden. weili.xu@ki.se
authors.forename: Weili
authors.initials: W
authors.lastname: Xu
authors.forename: Chengxuan
authors.initials: C
authors.lastname: Qiu
authors.forename: Margaret
authors.initials: M
authors.lastname: Gatz
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Pedersen
authors.forename: Boo
authors.initials: B
authors.lastname: Johansson
authors.forename: Laura
authors.initials: L
authors.lastname: Fratiglioni
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications; D016022:Case-Control Studies; D003704:Dementia / Q000453:epidemiology / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004200:Diseases in Twins / Q000453:epidemiology; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology